Author Topic: Study NCI  (Read 10779 times)

Val

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #60 on: January 26, 2011, 11:24:32 PM »
I had time to call Dr. Maldarelli this afternoon about the study the CAA announced.  I first got his voice mail, but he returned my call quickly and spent about 1/2 hour on the phone with me, answering my variety of questions.  No arrogance whatsoever, VERY kind and easy to converse with.  I would have preferred a 2-3 hour conversation with him, of course, but kept my questions at this point to those of greatest concern to me. 

My "report" of the conversation below is based on my understanding of his answers, not a verbatim transcript of what he said.  And please don't construe anything below as an "official" NIH, NCI or BWG position on any topic -- this is just my understanding of what we discussed.  For anyone who doesn't want to wade through it all, I've bolded what I think are the most important points. 

The sample collection is not being "sponsored" by the BWG per se, but is related.  The samples to be drawn for this study will be blinded and sent to the labs involved in the BWG, including Judy at WPI, Frank Ruscetti's group in Frederick and Lo/Alter, as well as others who are participating in the search for testing methods that are sensitive, specific and support high throughput.  Again, the labs who will be testing the fresh samples will use their own preferred methods (me - aargh), to include serology as well as the various PCRs and other testing methods being developed or currently in use.  Switzer at the CDC is also participating.

He said that the retrovirologists involved are approaching this based on their experience with HIV.  I know this will make everyone angry and frustrated because we're perfectly happy with what our heroes are doing, but they (the NIH) are still looking for convergence on negative and positive samples, where the different labs involved get consistent results on even ONE of each, using their different methods.  They need a higher degree of convergence than the BWG labs have achieved so far, so this is yet another step in that research -- to collect 50 patient samples of sufficient quantity (I think he said 100 mL) for further testing by the different labs. 

They are continuing to work on this to develop two things: 

The first is a high-throughput screening test that is very sensitive, as they now have for the HIVs.  However, highly sensitive tests run the risk of identifying false positives (inaccurate positive test results).  But the value of a highly sensitive test, even if it yields some percentage of false positives, is that ideally it catches a very, very large percentage of people who actually are positive and doesn't miss anyone (i.e., give false negative results).

The second is a highly specific test -- one that is extremely accurate at identifying the presence of infection and rules out anyone with a false positive result from the initial screening test.  In the best of all worlds, the highly specific confirmatory test would also eventually give relatively quick results, on the order of a few days...

None of the above is new to us.  But I thought it was worth going over again, just to reiterate what they (the NIH/BWG) are searching for and what they've all been saying they need in order to do further disease-causality research, as well as the epidemiological research to identify prevalence of the infection(s).

They are looking for patients who have already been tested in the belief these will be the "sickest of the sick."  The thinking among the retrovirologists is based on what worked to find HIV and nail down the methods of testing for it.  The idea is that patients who have already sought testing, either from a private lab or by volunteering to participate in other studies, are likely to be a patient group that is really, really sick (my words) with ME/CFS, however it's defined, and so more likely to be infected with XMRV/friends than potential participants identified through other methods.  They are NOT, however, ruling out obtaining samples from patients who haven't been tested previously (more on that later), but prefer to collect the samples from people who have already selected themselves for testing, independently from the results.  He said that they are NOT looking to compare previous test results to what comes out of the tests done from this effort.  He said the preference for previously tested participants is based on the characteristics of this group of patients, rather than their previous test results. 

In fact, he was upset when I said that some of us were very concerned that the purpose of this study is to invalidate previous test results from our heroes at WPI, NCI-Frederick, FDA, NIH/Alter.  He said that's not the purpose of seeking patients previously tested as negative or positive at all, that our hero(ine) labs are fully aware of this study, are participating in it and that the samples WILL be shared with them for the testing.  (My thought -- this is actually kind of a nifty way to side-step the whole controversy/question of which diagnostic criteria will be used.  More on this later, too.) 

Another point I found interesting is that he said NIH did NOT write the announcement of this study, the CAA did.  He said that any patient recruitment announcement from the NCI would have to be approved by the NIH IRB, which did NOT review and approve the CAA blurb.  He  said they approached CAA to make them aware of the study because the CAA has so many members and is supportive of continuing this research.  (My sense here is the same one we've all had re: the new retrovirologists who are just getting into ME research, which is that they're clueless about the ME/CFS history and politics -- despite being highly experienced with obstreperous HIV patient groups.)

So, given that he was upset that we are concerned that this is an attempt to undermine and/or invalidate the WPI and our other heroes, and he said that our heroes are willingly participating in this (obviously, they wouldn't, if they were concerned that it was a conspiracy to undermine them), I am REALLY wondering HOW this statement got into the announcement: "The researchers are specifically trying to reach individuals who have already been tested for XMRV so they can compare the results of their new tests with the results obtained using other tests."

MY question is, if the reason for wanting patients who have already sought out testing is because they are likely to be really sick, then how the hell did that statement get into the announcement and WHAT is the CAA up to with it???  OR, are there others involved in this study or higher up in management who DO have this agenda and communicated it to the CAA?  (Obviously, I believed Dr. Maldarelli's explanation of why they'd prefer to have patients who have already sought out testing, so, Gerwyn, I'm fully prepared for you to call me "naive," among other names.) 

So, that's the most important stuff I wanted to share about the conversation.  I have additional thoughts/speculations I'll post next.

 


rebecca

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #61 on: January 26, 2011, 11:50:27 PM »
Val, thank you so much for posting this extremely valuable information.

Quote
They are looking for patients who have already been tested in the belief these will be the "sickest of the sick."


If anyone has follow-up contact w/ Dr. Maldarelli, he should be told that the only way to get samples from "the sickest of the sick" is to send phlebotomists into their homes and bedrooms. 

Even if we eventually conclude that this study is worthy of our blood, it would be absolutely impossible for me and other severe patients to participate given the requirement of travel to Bethesda.  Even traveling to a local doctor would be nearly impossible for me. 

The travel requirement will attract the most functional patients, who likely have a low or undetectable viral copy number in their blood.

Gerwyn

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #62 on: January 26, 2011, 11:56:58 PM »


if the wpi is involved then they dont need to recruit people they have access to all the clinically positive samples they need.

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #63 on: January 27, 2011, 12:04:24 AM »
And if they want people who have not necessarily been tested but who are the sickest of the sick, all they need to do is contact the Dr. Cheney, Dr. Bell, Dr. DeMeirler and the other M.E. specialists.
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Val

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #64 on: January 27, 2011, 12:13:17 AM »
Dr. Maldarelli was very apologetic that they haven't nailed down the testing methods yet.  He said, in general, retrovirologists have been wanting to dive into this new area of research and are frustrated that it's turning out to be more complicated than they'd have ever foreseen.  He said he is sure that's it's extremely difficult for us to have the results and papers coming out at such a slow rate, with such ups and downs -- and particularly because the scientists had been so optimistic that they'd have the methods standardized much sooner than this, and would be on to disease-causality and epidemiological research by now.  I'm just adding this tidbit because I thought it was nice that someone inside NIH other than our heroes, recognizes how tough this is for us.

I said something along the lines that we patients and carers are grateful that NIH is doing biomed research into our disease, and what a difference it had made to us when Dr. Alter made his final statements at the BPAC meeting.  Dr. Maldarelli said that, in the view of many, Dr. Alter should be regarded as "a national treasure," not only because of his huge accomplishments, but also because he is never afraid to raise health concerns that he believes the federal government should be investigating. (I put quotation marks around "national treasure," because the phrase was so apt, but no quotes around the remainder because I'm not sure those were his exact words.)

This made me wonder the following, which is pure speculation and my thoughts only:

What if NIH is only funding this next step because Dr. Alter has "gone to the mat" for us?  What if NIH management still prefers to have all of this/us just go away, but feels they can't really get away with blowing off Dr. Alter (and hopefully Dr. Ruscetti, who is also a heavy-weight, but not quite as heavy-weight yet as Dr. Alter)?

And what if NIH management has felt forced to fund this study, and not yet cancel the BWG or Lipkin's study, but are only giving it a niggling few pennies, in hopes this will make it all go away sooner? 

I didn't ask any of these questions, of course, but I do have the sense that this is being done on a shoestring.  Which would explain why they aren't paying patient travel expenses and, consequently, are looking for locals.  And why, as far as I know, they also aren't paying to have phlebotomists or the other personnel who will administer the various types of testing come to the patients' homes -- which is what they'd have to do to really recruit the sickest of the sick.  And, I'm wondering whether the money they have will only cover the collection and processing procedures, while the participating labs will have to come up with their own funds to do the actual tests (this would be VERY BAD, and I hope someone can check this out with Judy). 

Anyway, he was interested in having my daughter participate, even if we hadn't had the testing done yet.  I told him we'd ordered the test kit, but hadn't gotten it together yet to have her blood drawn.  So, perhaps the fact that we're intending to get her tested, one way or another, was sufficient to meet the "really, really sick enough to pay a lot of money out of pocket for tests that are still under development and won't lead immediately to any kind of treament" inclusion criteria.  At least it was enough that they'll be sending us the initial paperwork.   

We also discussed having me participate, either as a control or as a "we're not sure how to classify you but it would be interesting to see" case.  (I don't have ME by any criteria, just some FM symptoms.)

I'm still not sure if we'll actually do this, much more info to be obtained.  But I thought it was worth a call to see if I could get more info than what's in that awful CAA announcement.

Power just went out here (heavy, wet snow coming down), so I'm going to send this quick before it goes out for the night or whatever.

Gerwyn

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #65 on: January 27, 2011, 12:14:52 AM »
I had time to call Dr. Maldarelli this afternoon about the study the CAA announced.  I first got his voice mail, but he returned my call quickly and spent about 1/2 hour on the phone with me, answering my variety of questions.  No arrogance whatsoever, VERY kind and easy to converse with.  I would have preferred a 2-3 hour conversation with him, of course, but kept my questions at this point to those of greatest concern to me. 

My "report" of the conversation below is based on my understanding of his answers, not a verbatim transcript of what he said.  And please don't construe anything below as an "official" NIH, NCI or BWG position on any topic -- this is just my understanding of what we discussed.  For anyone who doesn't want to wade through it all, I've bolded what I think are the most important points. 

The sample collection is not being "sponsored" by the BWG per se, but is related.  The samples to be drawn for this study will be blinded and sent to the labs involved in the BWG, including Judy at WPI, Frank Ruscetti's group in Frederick and Lo/Alter, as well as others who are participating in the search for testing methods that are sensitive, specific and support high throughput.  Again, the labs who will be testing the fresh samples will use their own preferred methods (me - aargh), to include serology as well as the various PCRs and other testing methods being developed or currently in use.  Switzer at the CDC is also participating.

He said that the retrovirologists involved are approaching this based on their experience with HIV.  I know this will make everyone angry and frustrated because we're perfectly happy with what our heroes are doing, but they (the NIH) are still looking for convergence on negative and positive samples, where the different labs involved get consistent results on even ONE of each, using their different methods.  They need a higher degree of convergence than the BWG labs have achieved so far, so this is yet another step in that research -- to collect 50 patient samples of sufficient quantity (I think he said 100 mL) for further testing by the different labs. 

They are continuing to work on this to develop two things: 

The first is a high-throughput screening test that is very sensitive, as they now have for the HIVs.  However, highly sensitive tests run the risk of identifying false positives (inaccurate positive test results).  But the value of a highly sensitive test, even if it yields some percentage of false positives, is that ideally it catches a very, very large percentage of people who actually are positive and doesn't miss anyone (i.e., give false negative results).

The second is a highly specific test -- one that is extremely accurate at identifying the presence of infection and rules out anyone with a false positive result from the initial screening test.  In the best of all worlds, the highly specific confirmatory test would also eventually give relatively quick results, on the order of a few days...

None of the above is new to us.  But I thought it was worth going over again, just to reiterate what they (the NIH/BWG) are searching for and what they've all been saying they need in order to do further disease-causality research, as well as the epidemiological research to identify prevalence of the infection(s).

They are looking for patients who have already been tested in the belief these will be the "sickest of the sick."  The thinking among the retrovirologists is based on what worked to find HIV and nail down the methods of testing for it.  The idea is that patients who have already sought testing, either from a private lab or by volunteering to participate in other studies, are likely to be a patient group that is really, really sick (my words) with ME/CFS, however it's defined, and so more likely to be infected with XMRV/friends than potential participants identified through other methods.  They are NOT, however, ruling out obtaining samples from patients who haven't been tested previously (more on that later), but prefer to collect the samples from people who have already selected themselves for testing, independently from the results.  He said that they are NOT looking to compare previous test results to what comes out of the tests done from this effort.  He said the preference for previously tested participants is based on the characteristics of this group of patients, rather than their previous test results. 

In fact, he was upset when I said that some of us were very concerned that the purpose of this study is to invalidate previous test results from our heroes at WPI, NCI-Frederick, FDA, NIH/Alter.  He said that's not the purpose of seeking patients previously tested as negative or positive at all, that our hero(ine) labs are fully aware of this study, are participating in it and that the samples WILL be shared with them for the testing.  (My thought -- this is actually kind of a nifty way to side-step the whole controversy/question of which diagnostic criteria will be used.  More on this later, too.) 

Another point I found interesting is that he said NIH did NOT write the announcement of this study, the CAA did.  He said that any patient recruitment announcement from the NCI would have to be approved by the NIH IRB, which did NOT review and approve the CAA blurb.  He  said they approached CAA to make them aware of the study because the CAA has so many members and is supportive of continuing this research.  (My sense here is the same one we've all had re: the new retrovirologists who are just getting into ME research, which is that they're clueless about the ME/CFS history and politics -- despite being highly experienced with obstreperous HIV patient groups.)

So, given that he was upset that we are concerned that this is an attempt to undermine and/or invalidate the WPI and our other heroes, and he said that our heroes are willingly participating in this (obviously, they wouldn't, if they were concerned that it was a conspiracy to undermine them), I am REALLY wondering HOW this statement got into the announcement: "The researchers are specifically trying to reach individuals who have already been tested for XMRV so they can compare the results of their new tests with the results obtained using other tests."

MY question is, if the reason for wanting patients who have already sought out testing is because they are likely to be really sick, then how the hell did that statement get into the announcement and WHAT is the CAA up to with it???  OR, are there others involved in this study or higher up in management who DO have this agenda and communicated it to the CAA?  (Obviously, I believed Dr. Maldarelli's explanation of why they'd prefer to have patients who have already sought out testing, so, Gerwyn, I'm fully prepared for you to call me "naive," among other names.) 

So, that's the most important stuff I wanted to share about the conversation.  I have additional thoughts/speculations I'll post next.

 

I am not going to call you anything Val.it is however clear that the assays that are going to be used are unproven. The information is also contrary to the protocol established by the phase iii of the blood working group where the wpi are in charge of distribution of clinically positive samples.In the absence of a IRB and a written protocol approaching him without formal WPI approval would be most unwise.

I think we really need to concentrate on fact and not speculation which is unlikely to help anyone.

you  must do as you will however

MEkoan

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #66 on: January 27, 2011, 12:16:04 AM »

They are looking for patients who have already been tested in the belief these will be the "sickest of the sick."  The thinking among the retrovirologists is based on what worked to find HIV and nail down the methods of testing for it.  The idea is that patients who have already sought testing, either from a private lab or by volunteering to participate in other studies, are likely to be a patient group that is really, really sick (my words) with ME/CFS, however it's defined, and so more likely to be infected with XMRV/friends than potential participants identified through other methods.  They are NOT, however, ruling out obtaining samples from patients who haven't been tested previously (more on that later), but prefer to collect the samples from people who have already selected themselves for testing, independently from the results.  He said that they are NOT looking to compare previous test results to what comes out of the tests done from this effort.  He said the preference for previously tested participants is based on the characteristics of this group of patients, rather than their previous test results.

I find this illogical on their part, Val.  A large % of the "sickest of the sick" are poverty stricken and, therefore, unable to avail themselves of any test for which they must pay.



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Gerwyn

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #67 on: January 27, 2011, 12:19:32 AM »
Dr. Maldarelli was very apologetic that they haven't nailed down the testing methods yet.  He said, in general, retrovirologists have been wanting to dive into this new area of research and are frustrated that it's turning out to be more complicated than they'd have ever foreseen.  He said he is sure that's it's extremely difficult for us to have the results and papers coming out at such a slow rate, with such ups and downs -- and particularly because the scientists had been so optimistic that they'd have the methods standardized much sooner than this, and would be on to disease-causality and epidemiological research by now.  I'm just adding this tidbit because I thought it was nice that someone inside NIH other than our heroes, recognizes how tough this is for us.

I said something along the lines that we patients and carers are grateful that NIH is doing biomed research into our disease, and what a difference it had made to us when Dr. Alter made his final statements at the BPAC meeting.  Dr. Maldarelli said that, in the view of many, Dr. Alter should be regarded as "a national treasure," not only because of his huge accomplishments, but also because he is never afraid to raise health concerns that he believes the federal government should be investigating. (I put quotation marks around "national treasure," because the phrase was so apt, but no quotes around the remainder because I'm not sure those were his exact words.)

This made me wonder the following, which is pure speculation and my thoughts only:

What if NIH is only funding this next step because Dr. Alter has "gone to the mat" for us?  What if NIH management still prefers to have all of this/us just go away, but feels they can't really get away with blowing off Dr. Alter (and hopefully Dr. Ruscetti, who is also a heavy-weight, but not quite as heavy-weight yet as Dr. Alter)?

And what if NIH management has felt forced to fund this study, and not yet cancel the BWG or Lipkin's study, but are only giving it a niggling few pennies, in hopes this will make it all go away sooner? 

I didn't ask any of these questions, of course, but I do have the sense that this is being done on a shoestring.  Which would explain why they aren't paying patient travel expenses and, consequently, are looking for locals.  And why, as far as I know, they also aren't paying to have phlebotomists or the other personnel who will administer the various types of testing come to the patients' homes -- which is what they'd have to do to really recruit the sickest of the sick.  And, I'm wondering whether the money they have will only cover the collection and processing procedures, while the participating labs will have to come up with their own funds to do the actual tests (this would be VERY BAD, and I hope someone can check this out with Judy). 

Anyway, he was interested in having my daughter participate, even if we hadn't had the testing done yet.  I told him we'd ordered the test kit, but hadn't gotten it together yet to have her blood drawn.  So, perhaps the fact that we're intending to get her tested, one way or another, was sufficient to meet the "really, really sick enough to pay a lot of money out of pocket for tests that are still under development and won't lead immediately to any kind of treament" inclusion criteria.  At least it was enough that they'll be sending us the .initial paperwork.   

We also discussed having me participate, either as a control or as a "we're not sure how to classify you but it would be interesting to see" case.  (I don't have ME by any criteria, just some FM symptoms.)

I'm still not sure if we'll actually do this, much more info to be obtained.  But I thought it was worth a call to see if I could get more info than what's in that awful CAA announcement.

Power just went out here (heavy, wet snow coming down), so I'm going to send this quick before it goes out for the night or whatever.

Val that is all pure speculation. if you dont have ME why are you even interested in the study especially one using untested methodology

belcanto

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #68 on: January 27, 2011, 12:28:44 AM »
Thank you, Val, for taking the time and trouble to speak with Dr. Maldarelli and to share that conversation here with us.  I very much appreciate having as much information as possible, particularly from the lead researcher involved.

Dr. Maldarelli did not contact us here - it sounds like what the CAA published about his study is incorrect, almost designed to make patients suspicious.

If you want a conspiracy theory - maybe the CAA wanted to goad this forum into a very predictable negative response.  It certainly worked, if so.

Skepticism is a very healthy response after what this community has suffered over the years.  Rejection of everyone and everything that does not fit the "ideal" that the WPI represents is short-sighted. 

How about an open mind in looking at some of this proposed research?  It seems unlikely to me that everyone other than the WPI is "against" us and looking to trick us into something.

Any researcher/advocate who reads this forum will understandably not want to participate in any way.  Maybe not in our best interest.


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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #69 on: January 27, 2011, 12:30:17 AM »
Val,
Thanks for taking the time to call Dr. Maldarelli and share the info with us. I appreciate the effort.

jackie

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #70 on: January 27, 2011, 12:30:57 AM »
val - just read this...thank you very much for your efforts in contacting/discussing this w/dr maldarelli, and passing the info along to us...and thanks for offering your "speculations" as well! (much appreciated and i hope that something works out for your daughter)...jackie.

belcanto

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #71 on: January 27, 2011, 12:31:31 AM »
I think it is inappropriate to challenge someone's motivation like this.  Val has a sick daughter.  But even if she didn't, there are many reasons for people to be invested in these discussions.

MEkoan

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #72 on: January 27, 2011, 12:32:55 AM »
Val,

I am so rude!  I forgot to thank you!

Thank You!
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Gerwyn

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #73 on: January 27, 2011, 12:38:12 AM »

If they are using unproven methodology then they dont know that they can find any XMRV .how then are they in charge of distributing xmrv positive samples to the others.lo atler and the wpi  focus on all HGRVs.

 They have as many clinically positive samples as they need and have assays known to detect the viruses

 they want the sickest of the sick (which are house if not bed bound) and expect them to travel

this does not make sense to me

Jaz

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Re: Do not join study - Dr. Frank Maldarelli at the NCI
« Reply #74 on: January 27, 2011, 12:38:25 AM »
Thank you for calling Dr. Maldarelli and relaying all that information to us Val.

I do find it odd that this doctor is taking our suspicions personally.  I think of Leonard Jason when I apologized for getting on his case and him saying, "We're glad you care, are involved and want to be sure things are being done right for ME."  I've paraphrased that but you get the idea.

I think it's good we're skeptical too. 
The goal is not to bring your adversaries to their knees but to their senses. -- Gandhi